NCT02610075

Brief Summary

This Phase Ib study will identify the Maximum Tolerated Dose (MTD) of AZD1775 monotherapy when administered orally once daily (QD) or two times per day (BID) on Days 1 to 5 followed by 9 days of rest in 14-day cycles, or QD on a 5/2 dosing schedule (5 days on, followed by 2 days rest) in 21-day cycles in patients with locally advanced or metastatic solid tumours. Alternative treatment schedules may be explored if preliminary data suggest these would be more appropriate. The effect of food on single dose PK of AZD1775 will be assessed in 12 patients. In this sub-study, patients will receive a single oral dose of AZD1775 with 240 mL of water, once in the fasted state and once following a high-fat meal.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2015

Typical duration for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 17, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 20, 2015

Completed
11 days until next milestone

Study Start

First participant enrolled

December 1, 2015

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 26, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 26, 2018

Completed
Last Updated

July 3, 2023

Status Verified

June 1, 2023

Enrollment Period

2.4 years

First QC Date

November 17, 2015

Last Update Submit

June 30, 2023

Conditions

Locally Advanced Solid TumoursMetastatic Solid TumoursOvarian Cancer

Keywords

AZD1775Metastatic solid tumorsOvarian cancer

Outcome Measures

Primary Outcomes (3)

  • The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 14 day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours.

    The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.

    Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.

  • The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered once daily (QD) in 21-day cycles (5 days on, followed by 2 days rest) in patients with locally advanced or metastatic solid tumours.

    The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.

    Dose-limiting toxicities will be evaluated during the first cycle (21 days) of AZD1775 monotherapy treatment.

  • The incidence of dose-limiting toxicities (DLTs) associated with AZD1775 monotherapy administered twice daily (BID) in 14-day cycles (5 days on, followed by 9 days rest) in patients with locally advanced or metastatic solid tumours.

    The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than one-third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level. If one of the first 3 patients enrolled in a given cohort experiences a dose-limiting toxicity (DLT), at least 3 additional patents will be enrolled in that cohort. If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD.

    Dose-limiting toxicities will be evaluated during the first 2 cycles (28 days) of AZD1775 monotherapy treatment.

Secondary Outcomes (5)

  • Plasma concentration of AZD1775 in fasted condition

    Samples for AZD1775 PK analysis (fasted) will be taken on Cycle 1 Day 1 predose & 2 hr postdose, Cycle 1, Day 5 pre-dose & 1, 2, 4, 6, 8, & 10 hr post-dose. Samples will also be collected on Cycle 5, Day 3, 4, or 5 pre-dose & pre-dose every 3-5 Cycles.

  • Plasma concentration of AZD1775 when dosed with a high fat meal.

    Samples for AZD1775 PK food effect analysis will be taken 4 hours after dosing on Cycle 2 Day 1. Subjects will fast for 10 hours prior to dose and for 4 hours post-dose except for the high-fat meal 30 minutes post-dose.

  • The incidence of treatment-emergent adverse events (TEAEs) in patients with locally advanced or metastatic solid tumours.

    6 months

  • Best objective response (OR) to treatment will be assessed by dose level cohort according to RECIST v1.1 in patients with locally advanced or metastatic solid tumours.

    8 weeks

  • The incidence of QTc interval abnormalities in patients with locally advanced or metastatic solid tumours.

    28 days

Study Arms (1)

AZD1775

EXPERIMENTAL

This is a single-arm study in which all patients will receive AZD1775 orally. Patients will continue to receive treatment with AZD1775 until disease progression, intolerable toxicity, or discontinuation criteria are met.

Drug: AZD1775

Interventions

AZD1775DRUG

All patients will receive intervention with AZD1775 orally. Patients will continue to receive treatment with AZD1775 until disease progression, intolerable toxicity, or discontinuation criteria are met.

AZD1775

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Prior palliative radiation completed ≥ 7 days prior to the start of AZD1775 and recovered from any acute adverse effects.
  • ECOG PS score 0 or 1.
  • Baseline laboratory values:
  • ANC ≥1500/μL
  • Hemoglobin (HgB) ≥9 g/dL
  • Platelets ≥100,000/μL
  • ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.
  • Serum bilirubin WNL or ≤1.5 x ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
  • Serum creatinine ≤1.5 x ULN, or measured creatinine clearance ≥45 mL/min.
  • Females who are not of child-bearing potential and fertile females of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to, and on the day of starting study treatment.
  • Males willing to use at least one medically acceptable form of contraception for duration of study and for 3 months after treatment stops.
  • Predicted life expectancy ≥12 wks.
  • Age ≥18
  • Histologically or cytologically documented locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
  • Measurable or non-measurable disease according to RECIST v1.1.

You may not qualify if:

  • Use of a treatment drug 21 days or 5 half-lives (whichever is shorter) prior to AZD1775. For drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required.
  • Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to first dose of study treatment.
  • Major surgical procedures ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days.
  • Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
  • Inability to swallow oral medications.
  • Palliative radiation therapy completed ≤7 days prior to start of study drug.
  • Known malignant CNS disease other than neurologically stable, treated brain metastases.
  • Rx or non-Rx drugs or products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to dosing and withheld until 2 weeks after the last dose of study drug.
  • Patients should stop using herbal medications 7 days prior to first dose of study treatment.
  • Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2.
  • Unstable angina pectoris
  • Congestive heart failure
  • Acute myocardial infarction
  • Conduction abnormality not controlled with pacemaker or medication
  • Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Research Site

Scottsdale, Arizona, 85258, United States

Location

Research Site

Denver, Colorado, 80218, United States

Location

Research Site

Nashville, Tennessee, 32705, United States

Location

Related Links

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

adavosertib

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Study Officials

  • Gerald Falchook, MD

    Sarah Cannon Research Institute HealthOne, Denver, CO

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 17, 2015

First Posted

November 20, 2015

Study Start

December 1, 2015

Primary Completion

April 26, 2018

Study Completion

April 26, 2018

Last Updated

July 3, 2023

Record last verified: 2023-06

Locations

US(3)